Brazilian scientists break genetic code of Zika protein

Brazilian researchers have described the three-dimensional structure of the NS5 protein responsible for the replication ofZika virus in infected cells — an important step towards developing an antiviral drug.

To do this, they stimulated a bacterium to produce large quantities of the NS5 protein, which were then purified and separated from the other substances produced by the bacteria. The researchers then transformed copies of the protein into crystals and mapped the spatial location of the 9600 atoms that form its structure.

‘The study may be essential to developing new drugs with specific antiviral activity against Zika.‘

Guilherme Milanez, State University of Campinas

With thisdata, they built a detailed computer model of the structural organisation of all atoms of the protein. The complete findings werepublished in Nature Communicationsback in March this year.

‘The characterisation of the molecular structure of the NS5 will allow us a more precise definition of each molecule capable of linking with specific regions of the proteins and interrupting their activity,’ says physicist Glaucius Oliva of the Institute of Physics of São Paulo University and lead author of the research, which is supported by the Brazilian research foundation FAPESP.

Protein NS5 is capable of copying the virus’ RNA thousands of times until Zika breaks through cell walls, spreading through the body.

The protein is produced by viruses of the genus flavivirus, which cause diseases such as yellow fever, dengue fever and hepatitis C. Because of its crucial role for virus replication in the human body, it has long been subject to research aimed at the development of drugs that can disrupt its activity.

The maindrugcandidate is sofosbovir, commonly used against hepatitis C — and this could quickly become a therapeutic option against the Zika virus, says Oliva.

Biologist Guilherme Milanez, from the Institute of Biology at the State University of Campinas, believes the study may be ‘essential’ to developing new drugs with specific antiviral activity against Zika.

‘Because NS5 is produced by different flaviviruses, it is likely than a single drug [such as sofosbovir]will have antiviral activity against the dengue, hepatitis C and Zika viruses’, he pointed out.

However, Milanez warns that studies are still in the early stage of development and there is a long way to go until the final formulation of a drug.

The study, published in Nature Communications, is supported by the Foundation for Research Support of the State of Sao Paulo (FAPESP), one of the donors of SciDev.Net.